The polypeptide cytokine interleukin-1 (IL-1) is a critical mediator of inflammatory and overall immune response. To date, three members of the IL-1 family, IL-1.alpha., IL-1.beta. and IL-1ra (Interleukin-1 receptor antagonist) have been isolated and cloned. IL-1.alpha. and IL-1.beta. are proinflammatory cytokines which elicit biological responses, whereas IL-1ra is an antagonist of IL-1.alpha. and IL-1.beta. activity. Two distinct cell-surface receptors have been identified for these ligands, the type 1 IL-1 receptor (IL-1RtI) and type II IL-1 receptor (IL-1RtII). Recent results suggest that the IL-1RtI is the receptor responsible for transducing a signal and producing biological effects.
As mentioned above, IL-1 is a key mediator of the host inflammatory response. While inflammation is an important homeostatic mechanism, aberrant inflammation has the potential for inducing damage to the host. Elevated IL-1 levels are known to be associated with a number of diseases particularly autoimmune diseases and inflammatory disorders. Since Il-1ra is a naturally occurring inhibitor of IL-1, IL-1ra can be used to limit the aberrant and potentially deleterious effects of IL-1. In experimental animals, pretreatment with IL-1ra has been shown to prevent death resulting from lipopolysaccharide-induced sepsis. The relative absence of IL-1ra has also been suggested to play a role in human inflammatory bowel disease.